Foundation Medicine, a molecular information company on the forefront of bringing comprehensive cancer genomic analysis to routine clinical care, has provided its first product, the FoundationOne™ assay, to clinicians since June 2012. It uses next-generation sequencing (NGS) to interrogate hundreds of cancer related genes from routine tumor samples. Test results are provided in a report that aligns detected mutations with potentially relevant treatment options and clinical trials.

The company says its test, which is priced at $5,800, offers a fully informative genomic profile for solid tumors and provides a concise report to assist physicians in matching patients with the targeted drugs or clinical trials best suited for their unique cancer. The assay is currently used by more than 1,000 doctors, as well as by 15 companies developing cancer drugs.

The company has sparked considerable enthusiasm among investors. In January, Bill Gates joined a $13.5 million expansion of its Series B venture financing, along with Yuri Milner, the Russian billionaire who invested in Facebook and Zynga. Evan Jones, co-founder and former CEO of Digene, also invested, and has taken a seat on Foundation’s board.

That $13.5 million investment added onto the $42.5 million Foundation raised in its Series B round in September, bringing the total for the round to $56 million and about $100 million of total investment in the company since its 2009 founding. The investor syndicate also included Third Rock Ventures, Google Ventures, Kleiner Perkins Caufield & Byers, Roche Venture Fund, and LabCorp.

What investors see in the company’s approach to cancer genomics may be a giant step forward, one that bridges the gap between genomic information and its clinical utility by presenting in it a useful context.

“It is increasingly challenging for physicians to incorporate the latest molecular diagnostic tests to help guide treatment of cancer patients due to the growing number of molecular subtypes that are understood across tumor types,” the company says. It adds that as more targeted therapies are approved for new molecular subtypes, the number of tests that need to be performed on each patient to determine their subtype increases and very quickly exhausts the very small amount of tumor tissue that is available in routine, clinical samples.

While oncologists can access the My Cancer Genome website to try to match patient mutations with drug therapies, the barrage of information, and its interpretation can prove daunting. The site, which started two years ago and includes 51 contributors from 20 institutions, operates free of charge, and is managed by Vanderbilt-Ingram Cancer Center. It lists mutations in different types of cancer, as well as drug therapies that may or may not be of benefit. Most of the drugs are in clinical trials; a few have been approved by the Food and Drug Administration.

Oncologists agree. As William Pao, M.D., Ph.D., director of personalized cancer medicine at Vanderbilt University Medical Center, Nashville, said in an interview with The New York Times, “There are so many genes and so many mutations. The human brain can’t memorize all those permutations.”

Several tests are available that analyze tumors for single or several genetic anomalies. One test, developed by Abbott Laboratories in collaboration with Pfizer, identifies patients with a rare form of lung cancer linked to the anaplastic lymphoma kinase (ALK) gene.

Pfizer’s anticancer drug Xalkori (crizotinib) acts as an ALK and ROS1 (c-ros oncogene 1) inhibitor, and was approved for treatment of some non-small cell lung carcinomas by the FDA in just four years and based on studies in 255 patients, largely because the company could use the test to select patients most likely to benefit from the drug.

Growing information about genetics and cancer suggests that patients do not all respond to the same drugs. Still, testing patients for each and every genetic anomaly one at a time would be “very onerous, expensive, and time-consuming,” says Dr. Pao. “The nice thing about platforms like the one Foundation has is that it detects all of them at the same time.”

Searching for Drivers

What distinguishes Foundation Medicine’s approach from that of other genomic sequence test providers is that rather than looking for specific cancer markers, the company's test analyzes the entire coding sequence of 236 cancer-related genes often rearranged or altered in cancer. These genes are known to be somatically altered in human cancer based on current scientific and clinical literature. By looking at the entire genome, and putting together a summary report for the doctor on what’s normal and abnormal in the patient’s tumor, the hope is that Foundation’s approach will provide novel insights on which targeted drug or combination of drugs will show the most efficacy for the individual patient.

FoundationOne interrogates all genes somatically altered in human cancers that are validated targets for therapy or unambiguous drivers of oncogenesis based on current knowledge. It reveals all classes of genomic alterations including base substitutions, insertions, deletions, copy number alterations, and select rearrangements. Each patient’s genomic profile is reported to the physician matched with targeted therapies and clinical trials that may be relevant based on the molecular blueprint of their tumor.

Last year’s ASCO meeting offered results from two studies using NGS to provide actionable information about genomic tumor alterations in individual patients’ cancers across all solid tumor types. In one study, completed in collaboration with researchers at Dana-Farber Cancer Institute, researchers assayed cancer-relevant genes in 24 cases of non-small cell lung cancer (NSCLC). The researchers identified 50 genomic alterations in 21 genes using NGS, with at least one relevant alteration occurring in 83% of tumors. In 72% of the samples, at least one genomic alteration was associated with an available treatment or clinical trial of a targeted therapy.

Researchers also reported discovery of a novel, recurrent KIF5B-RET gene fusion, which occurred in tumors lacking all other known oncogenic driver alterations. KIF5B-RET, when introduced into Ba/F3 cells, showed IL-3 independent growth consistent with oncogenic transformation. The investigators concluded that preliminary sensitivity findings suggest clinical trials are warranted to investigate the effect of multi-kinase inhibitors of RET (sunitinib, sorafenib, and vandetinib) on tumors harboring the unique fusion.

In its collaboration with Sloan Kettering, Foundation Medicine said it will focus on co-development of a new molecular diagnostic product designed to match patients with hematologic cancers with the most rational targeted therapies or clinical trials for their cancer. Experts in hematology from Memorial Sloan-Kettering will help accelerate product development by providing clinical and genomic expertise.

This new test is being developed using RNA sequencing in addition to DNA sequencing, the company says, to better enable identification of the unique genes and classes of genomic alterations that are characteristic of hematologic malignancies.

Foundation Medicine added that it intends to commercialize the hematologic cancer test both in the United States and internationally. The company operates a CLIA-certified lab in Cambridge, MA, and receives clinical patient samples from academic medical centers and community hospitals the world over. The new test is expected to be commercially available by the end of this year.

As Christopher-Paul Milne, associate director of the Tufts Center for the Study of Drug Development told MIT’s Technology Review, reimbursement remains “one of the biggest impediments to personalized medicine.” But he also predicted that it’s just a matter of time before payers come around as the number of medications targeted to people’s DNA grows. “Once you get 10 drugs that require screening, or to where practitioners wouldn’t think about using a drug without screening first, the floodgates will open,” he says. “Soon, in cancer, this is the way you will do medicine.”

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